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Peripheral Gonadotropin-Inhibitory Hormone (GnIH) Acting as a Novel Modulator Involved in Hyperphagia-Induced Obesity and Associated Disorders of Metabolism in an In Vivo Female Piglet Model

Apart from the well-established role of the gonadotropin-inhibitory hormone (GnIH) in the regulation of the reproductive functions, much less is known about the peripheral role of the GnIH and its receptor in the metabolic processes. On account of pig being an excellent model for studies of food int...

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Autores principales: Chen, Lei, Zhang, Xin, Song, Xingxing, Han, Dongyang, Han, Kaiou, Xu, Wenhao, Luo, Rongrong, Cao, Yajie, Shi, Yan, Liu, Chengcheng, Xu, Changlin, Li, Zixin, Li, Yinan, Li, Xun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692342/
https://www.ncbi.nlm.nih.gov/pubmed/36430435
http://dx.doi.org/10.3390/ijms232213956
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author Chen, Lei
Zhang, Xin
Song, Xingxing
Han, Dongyang
Han, Kaiou
Xu, Wenhao
Luo, Rongrong
Cao, Yajie
Shi, Yan
Liu, Chengcheng
Xu, Changlin
Li, Zixin
Li, Yinan
Li, Xun
author_facet Chen, Lei
Zhang, Xin
Song, Xingxing
Han, Dongyang
Han, Kaiou
Xu, Wenhao
Luo, Rongrong
Cao, Yajie
Shi, Yan
Liu, Chengcheng
Xu, Changlin
Li, Zixin
Li, Yinan
Li, Xun
author_sort Chen, Lei
collection PubMed
description Apart from the well-established role of the gonadotropin-inhibitory hormone (GnIH) in the regulation of the reproductive functions, much less is known about the peripheral role of the GnIH and its receptor in the metabolic processes. On account of pig being an excellent model for studies of food intake and obesity in humans, we investigated the peripheral effects of the GnIH on food intake and energy homeostasis and revealed the underlying mechanism(s) in female piglets in vivo. Compared to the vehicle-treated group, intraperitoneally injected GnIH significantly increased the food intake and altered the meal microstructure both in the fasting and ad libitum female piglet. GnIH-triggered hyperphagia induced female piglet obesity and altered islet hormone secretion in the pancreas, accompanied with dyslipidemia and hyperglycemia. Interestingly, GnIH decreased the glucose transport capacity and glycogen synthesis, whereas it increased the gluconeogenesis in the liver, while it also induced an insulin resistance in white adipose tissue (WAT) via inhibiting the activity of AKT-GSK3-β signaling. In terms of the lipid metabolism, GnIH reduced the oxidation of fatty acids, whereas the elevated fat synthesis ability in the liver and WAT was developed though the inhibited AMPK phosphorylation. Our findings demonstrate that peripheral GnIH could trigger hyperphagia-induced obesity and an associated glycolipid metabolism disorder in female piglets, suggesting that GnIH may act as a potential therapeutic agent for metabolic syndrome, obesity and diabetes.
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spelling pubmed-96923422022-11-26 Peripheral Gonadotropin-Inhibitory Hormone (GnIH) Acting as a Novel Modulator Involved in Hyperphagia-Induced Obesity and Associated Disorders of Metabolism in an In Vivo Female Piglet Model Chen, Lei Zhang, Xin Song, Xingxing Han, Dongyang Han, Kaiou Xu, Wenhao Luo, Rongrong Cao, Yajie Shi, Yan Liu, Chengcheng Xu, Changlin Li, Zixin Li, Yinan Li, Xun Int J Mol Sci Article Apart from the well-established role of the gonadotropin-inhibitory hormone (GnIH) in the regulation of the reproductive functions, much less is known about the peripheral role of the GnIH and its receptor in the metabolic processes. On account of pig being an excellent model for studies of food intake and obesity in humans, we investigated the peripheral effects of the GnIH on food intake and energy homeostasis and revealed the underlying mechanism(s) in female piglets in vivo. Compared to the vehicle-treated group, intraperitoneally injected GnIH significantly increased the food intake and altered the meal microstructure both in the fasting and ad libitum female piglet. GnIH-triggered hyperphagia induced female piglet obesity and altered islet hormone secretion in the pancreas, accompanied with dyslipidemia and hyperglycemia. Interestingly, GnIH decreased the glucose transport capacity and glycogen synthesis, whereas it increased the gluconeogenesis in the liver, while it also induced an insulin resistance in white adipose tissue (WAT) via inhibiting the activity of AKT-GSK3-β signaling. In terms of the lipid metabolism, GnIH reduced the oxidation of fatty acids, whereas the elevated fat synthesis ability in the liver and WAT was developed though the inhibited AMPK phosphorylation. Our findings demonstrate that peripheral GnIH could trigger hyperphagia-induced obesity and an associated glycolipid metabolism disorder in female piglets, suggesting that GnIH may act as a potential therapeutic agent for metabolic syndrome, obesity and diabetes. MDPI 2022-11-12 /pmc/articles/PMC9692342/ /pubmed/36430435 http://dx.doi.org/10.3390/ijms232213956 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Lei
Zhang, Xin
Song, Xingxing
Han, Dongyang
Han, Kaiou
Xu, Wenhao
Luo, Rongrong
Cao, Yajie
Shi, Yan
Liu, Chengcheng
Xu, Changlin
Li, Zixin
Li, Yinan
Li, Xun
Peripheral Gonadotropin-Inhibitory Hormone (GnIH) Acting as a Novel Modulator Involved in Hyperphagia-Induced Obesity and Associated Disorders of Metabolism in an In Vivo Female Piglet Model
title Peripheral Gonadotropin-Inhibitory Hormone (GnIH) Acting as a Novel Modulator Involved in Hyperphagia-Induced Obesity and Associated Disorders of Metabolism in an In Vivo Female Piglet Model
title_full Peripheral Gonadotropin-Inhibitory Hormone (GnIH) Acting as a Novel Modulator Involved in Hyperphagia-Induced Obesity and Associated Disorders of Metabolism in an In Vivo Female Piglet Model
title_fullStr Peripheral Gonadotropin-Inhibitory Hormone (GnIH) Acting as a Novel Modulator Involved in Hyperphagia-Induced Obesity and Associated Disorders of Metabolism in an In Vivo Female Piglet Model
title_full_unstemmed Peripheral Gonadotropin-Inhibitory Hormone (GnIH) Acting as a Novel Modulator Involved in Hyperphagia-Induced Obesity and Associated Disorders of Metabolism in an In Vivo Female Piglet Model
title_short Peripheral Gonadotropin-Inhibitory Hormone (GnIH) Acting as a Novel Modulator Involved in Hyperphagia-Induced Obesity and Associated Disorders of Metabolism in an In Vivo Female Piglet Model
title_sort peripheral gonadotropin-inhibitory hormone (gnih) acting as a novel modulator involved in hyperphagia-induced obesity and associated disorders of metabolism in an in vivo female piglet model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692342/
https://www.ncbi.nlm.nih.gov/pubmed/36430435
http://dx.doi.org/10.3390/ijms232213956
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